This invention relates generally to methods for medical treatment and more particularly to the application of hypothermia by various means including by endovascular heat exchange to treat chronic heart disease. These methods find particular usefulness in treating congestive heart failure.
Chronic cardiac failure may occur over a long period of time and may result from many root causes: diabetes, high blood pressure, clogged coronary arteries, and even acute events such as heart attacks. Whenever a heart has inadequate output, the resultant problems are legion and often systemic. The diseases is progressive; because of the inadequate supply of oxygen-rich blood to fuel the body""s needs, people with heart failure often experience shortness of breath and uncommon fatigue with daily activities. Then as the condition progresses, the chambers of the heartxe2x80x94particularly the ventricles xe2x80x94become increasingly enlarged as the heart tries to compensate for the inefficiencies. Ultimately a complex process of damaging structural and functional changes to the heart result. The enlarged heart looses the ability to pump efficiently. There may be inadequate ability to handle venous return, leading to congested liver, water retention in the extremities and other problems of edema. There may be inadequate output from the left heart leading to congested lungs. There may be inadequate supply of oxygenated blood to various organs including the heart itself, and areas including the brain, leading to all the problems associated with hypoxia. There may be inadequate removal toxic metabolic waste products from organs or failure to clear drugs or toxic substances via the liver, leading to
The condition of heart failure is complex and may be diagnosed by any one or a number of different criteria: the cardiac output may be low, generally consideredbelow 2.5 liters per minute; the stroke volume of the heart may be low, for example below 25 cc; the ejection fraction of the sick heart may be below 40%; there may be echocardiographic findings of enlarged or improperly pumping hear; physical examinations including x-rays and stress testing may indicate cardiac failure; there may be cardiomegally; there may be increased left ventricular wall thickness and chamber dilation indicative of cardiac failure; there may be pulmonary edema, which with other sympotoms and findings may indicate cardiac failure; there may be angiographic findings indicative of heart failure; and a diagnostic test of blood components, such as electrolytes or proteins may indicate heart failure. This lis is not exhaustive of the symptoms and findings that may help diagnose heart failure, but is offered to show the extent to which heart failure impacts the entire patient and may radically deteriorate the patient""s life quality.
One common condition is congestive heart failure (CHF). CHF is one of the most serious health problems in the world. An estimated 4.8 million Americans alone have CHF. It is often the end stage of serious heart disease; half of those diagnosed with CHF will be dead within 5 years. An estimated 400,000 new case are diagnosed each year. It is the most common diagnosis in hospital patients age 65 years and older, with the disease affecting 10% of all those over the age of 70. The financial cost of treatment of CHF patients is over $17 billion a year. The human cost is beyond measure.
CHF is a complex clinical syndrome characterized by impaired ventricular performance, exercise intolerance, a high incidence of ventricular arrhythmias, and shortened life expectancy. It general, the heart is not pumping well enough to meet the body""s metabolic demands and to provide adequate venous return. CHF is generally the result of a long clinical process. A general description of the downward spiral is: from normal heart function, to asymptomatic left ventricular (LV) dysfunction, to compensated CHF, to decompensated CHF and finally refractory CHF.
In the patient with asymptomatic left ventricular dysfunction, the abnormality in function is usually detectable by laboratory testing only. As the disease progresses, the patient develops symptoms such as mild exercise intolerance indicating inadequate cardiac output during stress. Milder forms of therapy are required at this point, such as diuretics, vasodilators and digoxin. The heart compensates by dilating to increase the volume of blood ejected per beat to increase cardiac output. Over time, the heart grows in size (myocardial hypertrophy) but also dilates to become more flaccid and less able to pump efficiently.
As the disease progresses, the structural changes become inadequate to successfully compensate, and the patient decompensates and becomes symptomatic at rest. Aggressive therapy is required at this point, consisting of diuretics,vasodilators and potent inotropic agents. These inotropic agents can lead to a transient improvement in hemodynamics, but may also accelerate the degenerative process in the heart, and increase mortality. Once the patient becomes unresponsive to inotropic therapy, a period of refractory CHF ensues. Treatment options are then generally limited to mechanical support (e.g. LV assist devices) or cardiac transplantation.
When the sufferer of CHF enters this final stage and the cardiac disease is so severe that he or she needs a heart transplant to survive for any length of time, the outlook is grim. According to the United Network for Organ Sharing (UNOS), more than 40,000 patients were waiting for a heart transplant as of February of 2000, and only 2,235 people received a donated heart in 2000. The vast majority of those needing a heart transplant will die waiting.
One method of increasing the likelihood that the patient will survive to receive a heart transplant is to treat the patient""s heart with inotropic drugs or heart pacer to return it temporarily to an improved state and temporarily provide the patient""s body with improved cardiac output. This treatment regime has the severe disadvantages set out below, and is not always available, but when available does provide a temporary improvement that might forestall death.
Inotropic drugs are drugs that increase muscle contractility, and in particular the contractility of the heart muscle. The drugs available include digitalis glycosides, available for almost 200 years to increase the force of contraction in both normal and failing heart muscles, but these have a very narrow therapeutic range and are limited by toxic side effects. The patient may develop tolerance and these drugs loose their effectiveness and the dose must be increased. Eventually they may not be effective at all.
Another treatment for those with decompensated congestive heart failure is the administration of the inotropic drugs milrinone or dobutamine. These drugs cause the heart to pump more vigorously and perhaps more effectively and to lead to improved overall condition of the patient, temporarily, However, chronic administration of these inotropic drugs generally leads to worsened long term prognosis and increased mortality rates. It has been postulated that the increase in metabolic activity leads to the buildup of potentially harmful metabolic by-products and perhaps also artificially overrides the auto protective effect of hibernation of heart tissue. In any event, the administration of these drugs may lead to long term heart muscle deterioration and long term increased mortality. There may also be more immediate dangers: patient""s who receive inotropic drugs and show clinical improvement over the short term often have symptomatic and hemodynamic rebound leading to worsened heart failure during or shortly after being weaned from the inotropic drugs. As a result, these inotropic agents are only indicated for short-term intravenous administration in CHF patients who can be closely monitored and who have not responded well to digitalis, diuretics or vasodilators.
These intermittent periods of artificially increased heart output by drug therapy are sometimes referred to as drug holidays, that is the body is provided with a short term increase in cardiac output in order to maintain the patient until long term treatment is available. Refractory congestive heart failure is such a serious and dangerous problem that even such desperate measures may be justified. Several of these drug holidays may well be needed to ensure survival while a congestive heart failure patient waits for a suitable heart transplant donor. The short term improvement may be worthwhile to buy some time before the condition is once again grave and life threatening.
As with inotropic drugs, treatment with a heart pacer may lead to improvement in the short term, but the patient""s condition generally degenerates again over time and the patient may suffer long term cardiac damage or even death due to the artificial stimulation of the heart muscle. Nonetheless, the administration of heart pacer therapy is still sometimes applied to hemodynamically unstable patients to provide support until more effective long term therapy (e.g. heart transplant ) can be supplied. However, some method of achieving the short term benefits of inotropic therapy without the attendant long term disadvantages of the drugs or the pacer would be a great benefit.
Sometimes the patient""s condition, due to CHF or other cardiac failure, is so poor that the patient is not a candidate for needed treatment. This may be the case, for example, if the patient is in such unstable hemodynamic condition that he or she is not a candidate for needed revascularization intervention such as percutaneous cardiac intervention (PCI), usually angioplasty, or by pass surgery due to the risk of death. It is rather ironic that the very condition that needs to be corrected, cardiac insufficiency, causes the patient to be so unstable that he or she is not eligible for treatment. Some method to achieve short-term stabilization is needed to allow application of the therapy, and some method without the long term disadvantages of the drug treatment mentioned above would be highly desirable.
Sometimes a post-operative patient has a heart that is not recovering, and the failure of the heart to pump properly makes post operative recovery impossible. Because of patient condition, other drugs being used or already in the patient""s system, or other factors, the patient may not respond to or may not be eligible to receive inotropic drugs or mechanical pacing. In such a situation some other option would be of great value.
Mild hypothermia has been shown to both increase the contractility of the heart muscle and to reduce its metabolic requirements. Indeed, if the hypothermia is systemic, the metabolic demands of the entire body are generally reduced, so that the demands placed on the heart may be reduced. The present invention provides a method for treating the heart by application of mild hypothermia to increase the heart output and thus improve the overall condition of the patient. In general, the method comprises the steps of a) inducing hypothermia in the patient suffering from or in imminent danger of suffering form insufficient cardiac output; and b) maintaining the patient in the hypothermic condition for a sufficient time to provide a helpful amount of improved cardiac output. This method will also generally include the application of effective anti-shivering mechanisms. The method may also include the controlled re-warming of the patient.
Hypothermia is preferably induced by removing heat from the patient with a heat exchange apparatus. The heat exchange apparatus may be, for example a heat exchange catheter with a heat exchange region placed in the vasculature of the patient so that it directly exchanges heat with the blood flowing over the heat exchange region. Alternatively it may be a heat exchange catheter having a heat exchange region placed in the esophagus of a patient and exchange heat with blood with blood in the esophageal wall, or less directly, in the aorta through the esophageal and aortic walls. It may be a heat exchange catheter placed directly within the stomach. It may even be an enhanced method of cooling blood through the skin of the patient, as with a cooling blanket, cooling patch, or cooling tent, provided that whatever heat exchange method is used is fast and efficient enough to induce hypothermia sufficient to be therapeutic for the treatment of congestive heart failure and the user is able to control the shivering of the patient.
Patients may be given these hypothermic heart xe2x80x9cholidaysxe2x80x9d for periods of 3 hours, 12 hours, or even up to three days depending on the individual patient""s condition and needs. Since merely cooling a patient is fairly benign and the advantages may be quite dramatic, long lengths of hypothermic administration may be administered. When the patient is placed in a hypothermic condition, 1xc2x0 C. or more below normothermic, and the output of the heart increases, the overall condition of the patient improves significantly and the patient""s heart may receive sufficient additional blood and have a temporarily decreased metabolic need and decreased metabolic waste products so that it is able to recover to a healthier state and may even experience a reversal of heart damage as a result.
The danger of shivering is present whenever a patient is cooled below that patient""s shivering threshold, which in humans is generally about 35.5xc2x0 C. When inducing hypothermia below the shivering threshold, it is very important to control the shivering response. That response is so profound that it generates enough metabolic heat to overpower most cooling mechanisms, perhaps by as much as 200-600% over resting metabolic heat production (which also increases oxygen consumption by a similar amount, and generates a similar amount of potentially harmful metabolic by-products). In addition, the violent muscular activity that constitutes shivering is very stressful and generally very harmful to the patient suffering from congestive heart failure. Thus it is of great importance that shivering be avoided. This may be accomplished by the administration of certain drugs, and by the application of a warm blanket over the skin of the patient being cooled, and in many cases, both application of anti-shivering drugs and the application of a warming blanket. As can be seen, the application of surface cooling tends to exclude the possibility of application of a warming blanket, so for applications of hypothermia below the shivering threshold, generally endovascular hypothermia is preferable.
Once the patient has received the intended length of hypothermic treatment, the same heat exchanger used to induce the hypothermia may be used to re-warm the patient. This re-warming is generally a very slow and controlled re-warming. If the endovascular heat exchange catheter is under the automatic control of an external controller, perhaps in response to a temperature probe sensing the temperature of the patient, then the re-warming can be automatically started and the rate of re-warming controlled.
A second situation where this invention of using the application of mild hypothermia (32xc2x0 C.-35xc2x0 C.) to treat congestive heart failure is when a patient""s medical condition is too unstable because of congestive heart failure to allow treatment by reperfusion therapy or surgery. In these cases, the invention may be applied by a) cooling the patient to achieve mild hypothermia of the patient; b) monitoring the patient""s condition until the patient is sufficiently stable to permit the intervention or surgery; c) performing the intervention or surgery while the patient is maintained in a mildly hypothermic state; d) re-warming the patient in a controlled manner. A sensor of some patient parameter, such as pulse rate, oxygen consumption, blood flow, blood pressure or some combination of factors may be monitored, directly or automatically, to signal when the patient""s condition is appropriate for intervention or surgery. In this case, as when the hypothermia is applied as a therapy for congestive heart failure without intervention or surgery, the cooling and subsequent re-warming may be under direct or under automatic control based on feedback from the patient.
Further aspects and particulars of the present invention will become apparent to those of skill in the art upon reading and understanding of the detailed description and examples set forth herebelow.